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用于胶质瘤预后分层与治疗指导的弓形虫感染相关风险模型的开发与验证

英文原题:Development and Validation of a Toxoplasma Infection-Associated Risk Model for Prognostic Stratification and Treatment Guidance in Glioma.

查看英文原题

Development and Validation of a Toxoplasma Infection-Associated Risk Model for Prognostic Stratification and Treatment Guidance in Glioma.

PubMed 2026/04/17(内容时间) Biology (Basel) Q1 · IF 4.3(JCR 2025)

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中文摘要

胶质瘤是预后不良的侵袭性脑肿瘤。刚地弓形虫(T. gondii)相关转录程序对胶质瘤的贡献尚不清楚。我们从神经上皮细胞转录组中鉴定了T. gondii感染相关基因,将其映射到TCGA和CGGA胶质瘤数据集中,并通过RT-qPCR验证了其表达。通过Cox和LASSO回归构建了预后特征(TGRisk),并在独立队列中进行了验证。进行了功能、免疫和药物敏感性分析。共鉴定出40个感染相关基因,富集于应激反应、microRNA调控、核糖体生物合成和代谢。13基因TGRisk模型显著区分了高风险组和低风险组之间的生存。结合TGRisk与临床特征的列线图提高了预测准确性。高风险肿瘤显示免疫激活以及CD8 + T细胞、Tregs、巨噬细胞和中性粒细胞的更高浸润,而低风险肿瘤显示神经信号传导和NK细胞活性增强。药物敏感性预测提示低风险患者对temozolomide和bortezomib的反应更好,而高风险患者对dasatinib和ruxolitinib更敏感。

我们开发了一种新的T. gondii感染相关基因特征,可按预后、免疫特征和治疗脆弱性对胶质瘤患者进行分层。这些发现提示了宿主与T. gondii之间的相互作用,并为患者分层和个体化治疗提供了潜在生物标志物。

展开英文摘要原文

Gliomas are aggressive brain tumors with poor prognosis. The contribution of Toxoplasma gondii (T. gondii) -related transcriptional programs to glioma remains unclear.

We identified T. gondii infection-related genes from neuroepithelial cell transcriptomes, mapped them to TCGA and CGGA glioma datasets, and validated their expression via RT-qPCR. A prognostic signature (TGRisk) was constructed via Cox and LASSO regression and validated across independent cohorts. Functional, immune, and drug sensitivity analyses were conducted. Forty infection-related genes were identified, enriched in stress responses, microRNA regulation, ribosome biogenesis, and metabolism.

The 13-gene TGRisk model significantly separated survival between high- and low-risk groups. A nomogram combining TGRisk with clinical features improved prediction accuracy. High-risk tumors showed immune activation and higher infiltration of CD8 + T cells, Tregs, macrophages, and neutrophils, while low-risk tumors showed enhanced neuronal signaling and NK cell activity. Drug sensitivity prediction suggested low-risk patients were more responsive to temozolomide and bortezomib, whereas high-risk patients were more sensitive to dasatinib and ruxolitinib.

We developed a novel T. gongdii infection-related gene signature that stratifies glioma patients by prognosis, immune features, and therapeutic vulnerabilities.

These findings suggest host- T. gondii interactions and a potential biomarker for patient stratification and personalized therapy.

论文信息

作者
Pan L、Hu Q、Yu Q、Zhang X、Chen Y、Chen F、Deng W
单位
Yunnan Provincial Key Laboratory of Animal Nutrition and Feed, Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China.China
期刊
Biology2026 Apr 17
原文标识
PubMed 42041911 · DOI 10.3390/biology15080633